Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Sakarya University of Applied Sciences, Sakarya, Turkey; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 3K7, Canada.
Department of Medical Biology, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey; Department of Molecular Biochemistry and Genetics, Graduate School of Health Sciences, Hatay Mustafa Kemal University, Hatay Turkey.
Can J Physiol Pharmacol. 2020 Nov;98(11):763-770. doi: 10.1139/cjpp-2020-0009. Epub 2020 Jul 8.
Osteoarthritis (OA) is a degenerative disease affecting the majority of over 65 year old people and characterized by cartilage degeneration, subchondral abnormal changes, and inflammation. Despite the enormous socioeconomic burden caused by OA, currently, there is no effective therapy against it. Upper zone of growth plate and cartilage matrix associated protein (UCMA) is a vitamin K dependent protein and has a critical role in pathophysiological conditions associated with bone and cartilage. However, there is no research on the protective role of intra-articular UCMA treatment in OA pathogenesis. Therefore, we aimed to investigate the potential therapeutic role of UCMA in an in vivo model of OA. We report for the first time that intra-articular UCMA injection ameliorated cartilage degeneration in a monosodium iodoacetate induced OA rat model. Furthermore, the OA-induced activation of nuclear factor kappa B and bone morphogenetic protein 2 signals was attenuated by UCMA. Our results indicated that UCMA decreased cartilage oligomeric matrix protein levels but did not affect interleukin 6, total antioxidant status, and total oxidant status levels in the serum. In conclusion, UCMA exhibited a therapeutic potential in the treatment of OA. This protective effect of UCMA is possibly achieved by reducing the aggrecanase activity and the production of inflammatory cytokines.
骨关节炎(OA)是一种退行性疾病,影响大多数 65 岁以上的人群,其特征为软骨退化、软骨下异常改变和炎症。尽管 OA 给社会经济带来了巨大负担,但目前尚无有效的治疗方法。生长板上区和软骨基质相关蛋白(UCMA)是一种维生素 K 依赖性蛋白,在与骨骼和软骨相关的病理生理条件中具有关键作用。然而,目前尚无关于关节内 UCMA 治疗在 OA 发病机制中保护作用的研究。因此,我们旨在研究 UCMA 在 OA 体内模型中的潜在治疗作用。我们首次报道,关节内 UCMA 注射可改善碘乙酸钠诱导的 OA 大鼠模型中的软骨退化。此外,UCMA 减弱了 OA 诱导的核因子 κB 和骨形态发生蛋白 2 信号的激活。我们的结果表明,UCMA 降低了软骨寡聚基质蛋白水平,但对血清中的白细胞介素 6、总抗氧化状态和总氧化状态水平没有影响。总之,UCMA 在 OA 的治疗中表现出治疗潜力。UCMA 的这种保护作用可能是通过降低聚集酶活性和炎症细胞因子的产生来实现的。